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October 24, 2014

Professor seeks to understand the science of drug abuse through rats

Abraham Palmer (A.B. ’92), an associate professor in the Department of Human Genetics, has been awarded a $12 million five-year grant by the National Institute of Drug Abuse to study the genes that play a role in drug abuse in rats. Although Palmer and his team haven’t yet reached any conclusions, they hope to identify genetic regions and specific genes that are connected to drug abuse.

“We come to [our research] with the fundamental notion that some people are probably more genetically susceptible to drug abuse than others,” Palmer said. This means that to understand abuse and treatments for abuse, the team must first understand the genetic architecture that makes an individual predisposed to it. The research he is doing, though, is going to be conducted in rats.

One of the many keys to Palmer’s research is that, within the past four to five years, there have been advances in the research of the use of embryonic stem cells, and their role in rats, that allow researchers to inject rats with specific genetic material. From the early nineties until recently, much of the genetic testing had been done in mice due to the limited technology available to researchers. However, it is more difficult for mice to acquire the behaviors that Palmer and his team are interested in studying. “It’s a lot easier for us to teach a rat that if you press a lever you get [intravenous] cocaine,” he said.

Palmer and his lab are currently working on projects using cocaine and nicotine that they hope can shed light on the genetics of drug addiction. One looks at the fundamental genes that influence people and make them more susceptible to relapse. Another project looks at the social factors involved in smoking and how interactions with peer animals can influence the self-administration of nicotine.

Furthermore, Palmer’s lab will analyze gene expression in the parts of the rat’s brain that they know are impacted by drugs. In their studies, they look for the behavior of the rats when they come into contact with drugs, how the genes they have injected them with prior to conducting the tests play a role, and the possible biological factors that occur during drug consumption. “The reason [we] shifted a lot of research from mice toward rats is that the tools have recently come around that allow us to manipulate rat genomes that we have for a long time mouse genomes,” he said.

Palmer said that studying the genetics of human drug abusers is extremely hard for a variety of reasons. “One of the big impediments has turned out to be that a lot of the genetic variation that [is causal for drug abuse] is extremely rare…maybe unique to almost one individual [per] study.” But with rats, they “can breed [them] in a very systematic way so that [they] can create a situation where all of the genetic variants are somewhat common” so they can test hypotheses about drug abuse on a gene-by-gene basis.

In terms of looking ahead to future drug abuse treatments, “people are working on [the question of] how will you deliver either the replacement gene or the enzymes necessary to stitch that gene into the person’s genome,” Palmer said. Initially researchers would only be able to test people with very severe diseases like cystic fibrosis, due to safety concerns with gene alteration, but when, according to Palmer, “we have a level of safety with these procedures, we could move from these very severe cases where people’s lives are at stake…to increasingly less severe situations.” Situations like drug abuse.

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